The 2011 GOLD classification for COPD: Old GOLD vs. New GOLD Guidelines

Ever had a COPD patient with an awful FEV1, yet who seems to be cruising along, doing fine for years? How about a COPD patient with a relatively preserved FEV1, yet always seems to be in your clinic or the hospital? (See also: Review of GOLD 2017 COPD Guidelines)

Of course you have. We (clinicians and researchers) have recognized that the clinical behavior of individual patients with COPD is much more complex than is determined by the degree of airflow obstruction alone (i.e. FEV1). Since the first GOLD guidelines were published in 2001 (and updated in 2007) much research has gone into more meaningfully “phenotyping” patients with COPD, not only to help predict future clinical course, but also to aid in individualizing therapies. The BODE index demonstrated nicely how the incorporation of other clinical factors, including symptoms and functional capacity, could refine the prediction of mortality in patients with COPD beyond FEV1 strata. Further, COPD exacerbations are now recognized both as a clinically important outcome for therapeutic interventions and as a strong predictor of subsequent exacerbations and mortality.

Therefore, the 2011 GOLD guidelines, which consider symptoms and exacerbation history in addition to the degree of airflow obstruction for classifying patients, are a welcome update and a potential advancement in the clinical care of patients with COPD. Whether this system proves to be an improvement upon the old system requires more research. Two recent studies (reviewed below) begin to clarify how the new GOLD system, applied to broad populations of COPD patients, reclassifies risk and further characterizes patients in a way that may have important management implications.

Note thatthe assessment starts with categorization by symptom burden, and then is refined by “risk” evaluation using FEV1 and/or exacerbation history. Functionally, this means that patients can be categorized intothe higher risk groups (C and D) by either low FEV1 or frequent exacerbations, or both. The GOLD 2011 document further details a suggested initial management approach to patients in each GOLD grade (in addition to lots of other good stuff).

How GOLD 2011 Performs: The Danish and Spanish Studies

Two recent studies evaluated the new GOLD system in large cohorts of patients with COPD. Both wereretrospective analyses of cohorts prospectively enrolled for other reasons. This retrospective nature limited the accuracy and collection of some patient characteristics and outcomes. For example, in both studies, investigators had to figure out ways to look back for certain variables such as exacerbations that weren’t prospectively recorded.

That said, here’s a breakdown of the two study populations and their major findings:

The Danish study cohort was drawn from two population-based cohorts in Denmark and included a total of 6,628 patients meeting spirometric criteria for COPD. Because participants were enrolled from the general population, many were not previously identified as having COPD and were not on COPD medications. Both inpatient exacerbations (acute hospitalizations for COPD) and outpatient exacerbations (short courses of steroids with or without antibiotics) were identified using national registries and diagnostic codes. The mMRC dyspnea scale was used for symptom classification. Follow-up time averaged 4.3 years. Outcomes included all-cause mortality, cause-specific mortality, and exacerbations.

The Spanish study included 3,633 patients drawn from clinical cohorts enrolled at 11 centers in Spain. Therefore these patients generally had more severe disease. Notably, they were almost entirely men (93%). This study also used the mMRC for symptom classification (sorry CAT). In contrast to the Danish study, only inpatient exacerbations (acute hospitalizations for COPD) were recorded, thus missing milder exacerbations treated in the outpatient realm. There were more issues with missing data, and cause of death and exacerbation outcomes were not reported. Follow-up time was long, with outcomes reported up to 10 years.

Distribution of patients

In the Danish study, the majority of patients had mild disease by both GOLD systems (old GOLD 1 and new GOLD A) because this cohort was drawn from the general population, but the new GOLD “shifted” patients to both less and more severe disease categories (i.e. toward GOLD A and GOLD D, respectively). About 77% of patients were GOLD A, 14% were GOLD B, 4% were GOLD C, and >4% were GOLD D. Also, new GOLD groups B and D (more symptoms) tended to be older than GOLD groups A and C (less symptoms).

In contrast, in the Spanish study, the majority of patients were old GOLD 2 (44.8%) & 3 (34.9%) because these patients were recruited from the clinical setting rather than the general population. Similar to the Danish study, patients were “shifted” to GOLD A and D in the new system (1/3 each were classified as A and D; 1/6 each were classified as B and C). In other words, both studies demonstrated a “polarizing” re-classification effect of the new GOLD system.This distribution is probably the breakdown we’re more likely to see (compared to that of the Danish study) as pulmonologists.

Exacerbation risk

Only the Danish study reported on future exacerbation risk. New GOLD predicted future exacerbations much better than old GOLD(accuracy by C-statistic of 70% versus 59%), which is not surprising considering that past exacerbations predict future exacerbations.

Mortality risk

In both studies, mortality increasedstepwise as expected for old GOLD 1 to 4. However, in the Danish study, mortality risk in new GOLD increased out of order from A (3.8% at 3 years) to C (8.2%) to B (10.6%) to D (20.1%). This was at least partially driven by a higher risk for cardiovascular and cancer-related death in GOLD grades B and D (those with more symptoms) compared to GOLD grades A and C (those with less symptoms), suggesting that those with more symptoms may have a higher burden of comorbidities (by frequency and/or severity). In the Spanish study, there was no difference in survival between new GOLD grades B and C for up to 3 years, but survival curves did separate thereafter favoring improved survival of B compared to C. Comorbidity distribution was not reported.Bottom line:new GOLD was no better at predicting mortality than old GOLD.

GOLD C and D subgroups:

Remember that in new GOLD, patients can be classified into the “higher risk” categories C and D because of low FEV1 (<50%), frequent exacerbations (2 or more/year), or both. So does it matter how they get there? Well, in the Danish study, more patients were classified into GOLD C and D for low FEV1 alone (77%) than for history of exacerbations alone (17%) or both (6%). Those categorized by frequent exacerbations only, tended to be non-smokers and women. Those categorized by exacerbation history had a higher rate of future exacerbations (not surprising) than those categorized by low FEV1, while those categorized by low FEV1 tended to have higher mortality rates than those categorized by exacerbation history. The Spanish study showed a similar trend in mortality, and those categorized into grades C and D by low FEV1 AND frequent exacerbations had higher mortality than those categorized by either criterion alone.

GOLD Guidelines for COPD: What It All Means

Is GOLD 2011 platinum? Probably not, but it is an important update, at least conceptually, because it highlights the importance of clinical factors beyond FEV1 that may help us better predict disease course and better tailor our management strategies for COPD. Whether or not you are able to remember the ABCD system right away is probably not as important as just remembering to take into account symptoms and exacerbations.

The major take-away points for the behavior of the new GOLD classification system are:

GOLD 2011 does not appear to offer an overall advantage over the older system for predicting mortality in COPD, but it does reclassify risk for some patients. The intermediate risk groups (B and C) seem to have similar, or even reversed, mortality risk partially due to the higher symptom and co-morbidity burden of B patients compared to C patients. The higher risk C and D groups comprise a heterogeneous group, with mortality risk depending on whether patients are assigned to this group by frequent exacerbations, low FEV1, both.

GOLD 2011 does predict COPD exacerbations better than the older system, primarily because patients with past exacerbations are more likely to have future exacerbations. You could argue that prediction of exacerbations might be more clinically relevant than mortality prediction in the day-to-day management of COPD patients since we have pharmacotherapiesthat are proven to reduce exacerbations (e.g. inhaled corticosteroids/long-acting beta-agonists combinations and long-acting anticholinergics) but not mortality (other that smoking cessation, which should be offered to all, and oxygen use, which has specific indications).

Symptoms matter. Symptom severity predicts survival; symptoms can be improved by available therapies (e.g. bronchodilators); and more severe symptoms, especially symptoms out of proportion to the severity of airflow obstruction, should prompt a search for comorbidities that may be playing a role, in particular cardiovascular disease and possibly cancer.

While the GOLD update makes very reasonable treatment recommendations based on the new classification system, we must remember that clinical trials to date have been largely designed to enroll patients based on the older system (i.e. by FEV1 criteria). Whether the new system truly identifies subgroups that benefit more or less from available and experimental therapies will remain an endeavor of future research.

Perhaps future iterations of the GOLD classification will expand these concepts by separating out the exacerbation and airflow obstruction dimensions and by adding new dimensions such as comorbidities and functional limitation.